UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
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Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline.
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PMID:Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. 176 71

The butyrophenone neuroleptic haloperidol (10.65-85.2 microM) blocked the indirectly elicited twitch response of rat phrenic nerve diaphragm preparation. The depression was poorly reversible and was not mediated through dopamine receptors since neither dopamine nor apomorphine could alter the haloperidol blockade. Experiments on the isolated phrenic nerve indicated that the excitability of the nerve was blocked by haloperidol (42.6 microM) and that this blocking effect was minimized in presence of a high concentration of Ca2+ (5 mM) in the bathing fluid. Haloperidol (10.65-85.2 microM) also concentration-dependently inhibited acetylcholine (2.7 microM) contracture, without affecting the potassium chloride (0.5 M) and caffeine (15 mM) contracture. We conclude that haloperidol acts as a local anaesthetic on the motor nerve, probably by affecting calcium channels.
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PMID:Haloperidol on rat phrenic hemidiaphragm. 177 33

Malignant hyperthermia syndrome (MHS) is rare, inherited, and triggered by volatile anesthetics and depolarizing muscle relaxants. While potentially fatal, if recognized and treated early recovery is usual. However, the condition is often not recognized until an extreme increase in temperature develops with profound circulatory depression. In this stage the syndrome is irreversible, despite specific treatment with dantrolene. At present, the only reliable diagnostic test for susceptibility to malignant hyperthermia requires sampling of viable muscle for in vitro contracture tests with caffeine and halothane. Until our malignant hyperthermia diagnostic center was opened, such tests could not be performed in Israel. Since then we encountered a 22-year-old man who developed the partial picture of malignant hyperthermia syndrome during anesthesia for inguinal herniorrhaphy. He received dantrolene and recovered. 4 months later in vitro contracture tests with caffeine and halothane performed on biopsied muscle confirmed the diagnosis.
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PMID:[In vitro diagnosis of malignant hyperpyrexia syndrome]. 179 53

1. The effects of complete metabolic inhibition on excitation-contraction coupling in heart were studied by exposing patch-clamped guinea-pig ventricular myocytes, loaded via the patch pipette with the Ca2+ indicator Fura-2 (0.1 mM), to carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 1 microM) and 2-deoxyglucose (2-DG, 10 mM) while simultaneously recording membrane current, Fura-2 fluorescence, and cell motion. The patch pipette solution contained Cs+ and TEA (tetraethylammonium) to partially block K+ currents. 2. During voltage clamps from a holding potential of -40 mV to a test potential of 0 mV, complete metabolic inhibition decreased the Ca2+ current (ICa), activated the ATP-sensitive K+ current, modestly elevated diastolic [Ca2+]i and markedly reduced the [Ca2+]i transient without altering its voltage dependence. Active shortening was impaired and diastolic cell length decreased prior to large increases in diastolic [Ca2+]i, consistent with rigor induced by ATP depletion. Return of the [Ca2+]i transient to baseline and relaxation upon repolarization were also delayed. 3. Despite the depression of the peak [Ca2+]i transient induced by membrane depolarization during metabolic inhibition, the [Ca2+]i transient induced by a rapid exposure to 5 mM-caffeine was greater than control. The Na(+)-Ca2+ exchange current during the caffeine-induced [Ca2+]i transient was not affected by metabolic inhibition. 4. [Ca2+]i transients depressed by metabolic inhibition could be enhanced by augmenting ICa with elevated [Ca2+]o (10 mM) and Bay K 8644 (5 microM). 5. To study the relationship between the magnitude of ICa and the amplitude of the [Ca2+]i transient, ICa was modulated either by (a) voltage clamping the cell to different membrane potentials at constant [Ca2+]o or by (b) rapidly altering [Ca2+]o immediately prior to a voltage clamp to a fixed membrane potential. Under control conditions, the relationship between the size of ICa and the magnitude of the [Ca2+]i transient was the same whether ICa was modulated by altering membrane potential or [Ca2+]o, suggesting that membrane potential does not significantly modulate the Ca(2+)-induced Ca2+ release mechanism of cardiac excitation-contraction coupling. 6. After metabolic inhibition, however, the same ICa released less Ca2+ than under control conditions, consistent with some impairment of the Ca2+ release mechanism. 7. These results suggest that under conditions in which excitability is maintained by controlling membrane voltage and minimizing metabolically sensitive K+ currents, the decreased [Ca2+]i transient observed during metabolic inhibition severe enough to induce rigor is caused primarily by depression of ICa and not by depletion of intracellular Ca2+ stores. Additional factors also modestly hinder Ca2+ release from intracellular stores during metabolic inhibition.
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PMID:Mechanisms of excitation-contraction coupling failure during metabolic inhibition in guinea-pig ventricular myocytes. 182 31

The spike after-hyperpolarization (AH), which is linked to the Ca-activated K conductance system, in the rat superior cervical ganglion was examined by means of intracellular recording. The AH was shortened during repetitive stimulation of the cell at 1 Hz and reached a steady state within 10 sec. These changes in the AH disappeared after a part of the AH was depressed by 5 microM ryanodine. The steady state of AHs was dependent on the frequency of stimulation ranging from 0.005 Hz and 2 Hz: half depression was observed at 0.53 Hz. Half recovery time from the depression induced by conditioning stimuli at 2 Hz was approximately 14 sec. Caffeine (1 mM) or TEA (3 mM) enlarged the AH at low stimulation frequencies. Caffeine slightly shifted the frequency depressing the AH toward high frequencies, and TEA did not cause significant changes. These results suggest that the repetitive firing of cells decreases the intracellular Ca release by contributing to the generation of the AH, rather than by accelerating the loading of Ca to its storage sites.
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PMID:Ryanodine suppresses the frequency-dependent component of the spike after-hyperpolarization in the rat superior cervical ganglion. 185 25

Caffeine engenders qualitatively different subjective effects in humans at low and high doses. Low doses of caffeine are mildly reinforcing and produce psychomotor stimulation. High doses of caffeine can produce subjective feelings of anxiety, dysphoria and depression. The present study was designed to model these different subjective states in rats using a discrete trial shock avoidance/escape drug discrimination paradigm. Rats were trained to discriminate between i.p. injections of saline and either 10 or 56 mg/kg of caffeine. Rats trained at 10 mg/kg of caffeine acquired the discrimination in an average of 93 sessions and generalized completely to a variety of xanthine and nonxanthine behavioral stimulants including: d-amphetamine, apomorphine, 7-(beta-chloroethyl)theophylline, 9-chloro-2-(2-furanyl)-5,6-dihydro-1, 2,4-triazolo[1,5-c]quinazolin-5-imine (CGS 15943), cocaine, 1,7-dimethylxanthine, diethylpropion, beta-hydroxyethyltheophylline, methylphenidate, phenidimetrazine and theophylline. Rats trained at 56 mg/kg of caffeine acquired the discrimination in an average of 43 sessions and generalized completely only to theophylline. A variety of drugs representing diverse pharmacologic classifications including: benzodiazepine inverse agonists, pentylenetetrazol, yohimbine, ethylketocyclazocine and phencyclidine, were not generalized from either training dose, demonstrating the pharmacologic specificity of the discrimination. The discriminative effects of 10 mg/kg of caffeine appear to derive from a state of behavioral arousal, possibly mediated by catecholamines, and parallel the subjective effects produced by low doses of caffeine in humans. The discriminative effects of 56 mg/kg of caffeine are qualitatively different from those of 10 mg/kg but cannot be defined further at this time.
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PMID:Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. 189 Jun 22

1. Single, intact muscle fibres from the flexor brevis foot muscle of the mouse have been fatigued at 25 degrees C by 350 ms, 70 Hz stimulation trains, initially delivered every 3.8 s and then at stepwise decreasing intervals until tension was down to about 30% of the original (Po). Rested fibres generated a specific force of 372 +/- 8.4 kPa (mean +/- S.E.M., n = 25). 2. Endurance, defined as time to attain 0.5 Po, varied from 2.5 to 24 min, with the majority of fibres falling in the range 4-8 min, corresponding to 70-160 tetani. In all fibres where it was followed, tension recovery after cessation of stimulation was 90% or better. 3. Tetanic force declined in a characteristic way during fatiguing stimulation: initially tension fell to about 0.85 Po during eight to fourteen tetani (phase 1), then followed a long period of nearly steady tension generation (phase 2) and finally there was a rapid force decline (phase 3). 4. Caffeine (15 or 25 mM) caused a slight potentiation of tetanic force in the rested state (4.7 +/- 0.9%, n = 21) and slowed relaxation. No change in resting tension was seen with caffeine at concentrations up to 25 mM. 5. Caffeine (15-25 mM) caused a rapid and dramatic increase in tetanic force when applied to severely fatigued fibres: force output rose from 29.8 +/- 1.5 to 82.5 +/- 1.2% (n = 13) of Po. During phase 2 force potentiation with caffeine was much smaller. 6. A 10 s pause resulted in a large, transient force increase when imposed during phase 3 but had little effect on force production during phase 2. 7. Intracellular acidosis, induced by superfusion with Tyrode solution gassed with 30% CO2 instead of the normal 5% (extracellular pH 6.5 vs. 7.3), resulted in a fall in tetanic tension to about 0.85 Po (n = 7). This depression could to some extent be counteracted by 15 mM-caffeine, which brought tension back to about 0.90 Po. 8. It is concluded that there are at least two mechanisms for force decline during fatiguing stimulation: one which manifests itself early and is likely to be related to cross-bridge function and another representing deficient Ca2+ handling which becomes prominent at a later stage. For severe fatigue (0.3 Po) the latter mechanism is dominant.
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PMID:Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle. 190 15

Several classes of medications have been used to treat generalized anxiety disorders (GAD). Antidepressants are useful for chronic subpanic anxiety and anxiety associated with depression. Benzodiazepines are generally safe, but recent research suggests that the incidence of chronic abstinence syndromes may be higher than has been suspected. This class of medications is best used for circumscribed periods of time. Because buspirone has no significant interactions, it does not prevent benzodiazepine withdrawal and cannot be directly substituted for this class of medications. beta-Blockers are used when cardiovascular symptoms and tremor are prominent, for stage fright (propranolol) and possibly for social phobia (atenolol). Antihistamines have been used for elderly patients and for those with a history of substance abuse. Neuroleptics should only be prescribed for anxiety associated with psychosis, psychotic and possibly severe depression, and borderline personality disorder. Drug treatment of GAD should be used as part of a comprehensive treatment plan that includes assessment for medical illnesses that can aggravate anxiety, withdrawal of all unnecessary medications (especially CNS depressants) and caffeine, structured relaxation techniques, evaluation of the specific type of anxiety, and psychotherapy.
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PMID:Generalized anxiety disorder: new concepts and psychopharmacologic therapies. 196 48

We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol) ethanol (ETOH) on 1) the cytosolic [Ca2+] (Cai) transient measured as the change in indo 1 fluorescence at 410/490 nm and contraction elicited by electrical stimulation of single cells and 2) the sarcoplasmic reticulum (SR) Ca2+ content in cell suspensions. During stimulation at 1 Hz, clinically relevant ETOH correlations (0.1-0.15% [vol/vol]) caused a 10-15% decrease in the contraction amplitude, measured by myocyte edge tracking, without decreasing the Cai transient that initiates contraction. At higher ETOH concentrations (1-5% [vol/vol]), ETOH caused profound contractile depression and also reduced the magnitude of the Cai transient. These effects were reversed within minutes of ETOH washout. Addition of norepinephrine (10 microM) to the bathing solution or an increase in bathing [Ca2+] in the continued presence of ETOH could also reverse its effects. The relation of the amplitude of the Cai transient to the contraction amplitude measured across a range of bathing [Ca2+] was shifted by ETOH, such that for a given Cai transient a marked reduction in contraction amplitude occurred. In unstimulated myocyte suspensions, ETOH (1-5% [vol/vol]) caused a concentration-dependent depletion of SR Ca2+ content, manifested as a diminution in the Cai increase elicited by caffeine in the presence of extracellular EGTA and no added Ca2+. Thus, in rat cardiac myocytes a reduction in the myofilament Ca2+ response, possibly due to a decrease in myofilament Ca2+ sensitivity, is a mechanism for contractile depression due to clinically relevant ETOH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes. 203 17

Experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats of Koletsky type; measurements were carried out in both sexes. The behaviour of control and drug treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show increased aversion towards open space and high in the elevated plus-maze (when the number of visits of centre and open arms is considered in the first session); the latter type of rats also show elevated total time of locomotor-exploratory activity in both sessions, reduced rate of intra-session habituation of locomotor-exploratory activity in both sessions, and decreased percentage of time spent head dipping in both sessions. Tranylcypromine treatment at the dose 5 mg/kg b. w. increased number of visits in centre and in open arms only in the second session in the normotensive males, and this drug shows decrease in the latter parameter in the second session in the genetically hypertensive females. Tranylcypromine increased time spent in centre and in open arms in the first session only in the genetically hypertensive males, in the second session this drug shows increase in time spent in centre and in open arms in the normotensive females and decrease in the genetically hypertensive females. Caffeine treatment at the dose 10 mg/kg b. w. remained without effect in both strains of rats and in both sessions in the elevated plus-maze, except the decrease in the number of entries in centre and in open arms in the first session in the normotensive females. Diazepam treatment at the dose 1 mg/kg b. w. shows "anxiolytic" effect i.e., increase number of visits and time spent in centre and in open arms in both sessions and in both sexes of the genetically hypertensive rats. Thus diazepam shown its "anxiolytic" effect in very profound and stable manner only in the animals which show CNS neurotransmitter abnormalities reminding the CNS neurochemical abnormalities in human forms of depression and anxiety. It is worthwhile to note that diazepam only in the latter mentioned strain of rats very profoundly elevates the percentage of time spent head dipping. Thus this drug elevates the reactivity towards stimuli which show biological sense for the rats, i. e., to look up the small and dark space. This type of reaction is decreased in the genetically hypertensive rats of both sexes relative to the control normotensive rats of Wistar strain.
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PMID:Validation of aversion towards open space and height as a measure of anxiety in the genetically based animal model of depression. 213 25

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